Laboratory of Food Microbiology and Leuven Food Science and Nutrition Research Centre, Centre for Food and Microbial Technology, Department of Microbial and Molecular Systems, Faculty of Bioscience Engineering, Katholieke Universiteit Leuven, Kasteelpark Arenberg 22, B-3001 Leuven, Belgium.
Nucleic Acids Res. 2011 Aug;39(14):5991-6001. doi: 10.1093/nar/gkr219. Epub 2011 Apr 19.
The Mrr protein of Escherichia coli is a laterally acquired Type IV restriction endonuclease with specificity for methylated DNA. While Mrr nuclease activity can be elicited by high-pressure stress in E. coli MG1655, its (over)expression per se does not confer any obvious toxicity. In this study, however, we discovered that Mrr of E. coli MG1655 causes distinct genotoxicity when expressed in Salmonella typhimurium LT2. Genetic screening enabled us to contribute this toxicity entirely to the presence of the endogenous Type III restriction modification system (StyLTI) of S. typhimurium LT2. The StyLTI system consists of the Mod DNA methyltransferase and the Res restriction endonuclease, and we revealed that expression of the LT2 mod gene was sufficient to trigger Mrr activity in E. coli MG1655. Moreover, we could demonstrate that horizontal acquisition of the MG1655 mrr locus can drive the loss of endogenous Mod functionality present in S. typhimurium LT2 and E. coli ED1a, and observed a strong anti-correlation between close homologues of MG1655 mrr and LT2 mod in the genome database. This apparent evolutionary antagonism is further discussed in the light of a possible role for Mrr as defense mechanism against the establishment of epigenetic regulation by foreign DNA methyltransferases.
大肠杆菌的 Mrr 蛋白是一种侧向获得的 IV 型限制内切酶，对甲基化 DNA 具有特异性。虽然 Mrr 核酸酶活性可以通过大肠杆菌 MG1655 中的高压应激来诱导，但它的（过度）表达本身并不会赋予任何明显的毒性。然而，在这项研究中，我们发现大肠杆菌 MG1655 的 Mrr 在鼠伤寒沙门氏菌 LT2 中表达时会引起明显的遗传毒性。遗传筛选使我们能够将这种毒性完全归因于鼠伤寒沙门氏菌 LT2 中内源性的 III 型限制修饰系统（StyLTI）的存在。StyLTI 系统由 Mod DNA 甲基转移酶和 Res 限制内切酶组成，我们揭示了 LT2 mod 基因的表达足以引发大肠杆菌 MG1655 中的 Mrr 活性。此外，我们能够证明 MG1655 mrr 基因座的水平获得可以导致鼠伤寒沙门氏菌 LT2 和大肠杆菌 ED1a 中内源性 Mod 功能的丧失，并且在基因组数据库中观察到 MG1655 mrr 和 LT2 mod 的密切同源物之间存在强烈的负相关性。这种明显的进化拮抗作用将根据 Mrr 作为防御机制对抗外源 DNA 甲基转移酶建立表观遗传调控的可能作用进行进一步讨论。
